Uniparental disomy (UPD) exclusion in embryos following Preimplantation Genetic Testing for Structural Rearrangements...

Area of Science:

• Reproductive Medicine and Genetics
• Assisted Reproductive Technologies
• Human Genetics and Genomics

Background:

• Uniparental disomy (UPD) occurs when both chromosomal copies originate from a single parent, potentially causing imprinting disorders.
• Couples with chromosomal translocations face increased risks of aneuploidy and UPD in their offspring.
• Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) is crucial for selecting chromosomally normal embryos but may not directly assess UPD.

Purpose of the Study:

• To evaluate the integration of Short Tandem Repeat (STR) analysis into PGT-SR protocols for assessing UPD risk.
• To determine the impact of STR-based UPD screening on selecting euploid embryos for transfer in couples with translocations involving imprinted chromosomes.

Main Methods:

• Three couples with balanced chromosomal translocations underwent PGT-SR.
• STR analysis was performed on trophectoderm biopsies of euploid embryos after Whole Genome Amplification (WGA).
• Haplotyping using STR markers specific to rearranged chromosomes was employed to detect heterodisomic and isodisomic UPD.

Main Results:

• Two couples achieved successful pregnancies with healthy births from euploid embryos confirmed to be UPD-negative.
• One euploid embryo, also UPD-negative, failed to implant, resulting in no pregnancy.
• The study demonstrated the feasibility of detecting UPD in embryos selected via PGT-SR.

Conclusions:

• Integrating STR-based UPD screening into PGT-SR workflows is a reliable and cost-effective method.
• This approach significantly enhances embryo selection by mitigating the risk of severe imprinting disorders like Prader-Willi and Angelman syndromes.
• The strategy offers a practical advancement for improving reproductive outcomes in families with chromosomal rearrangements.